Comparable overall rates of TEAEs and SAEs vs Aubagio® (teriflunomide)1

Overall, the proportion of patients experiencing at least 1 treatment-emergent adverse event (TEAE) or serious adverse event (SAE) was similar across treatment groups.1

Adverse reactions (ARs) reported in at least 5% of patients taking PONVORY™ and at a higher rate than in patients taking Aubagio®2

comparable rates of adverse reactions vs teriflunomide1

  • The most common ARs (incidence ≥10%) in patients taking PONVORY™ were upper respiratory tract infection (37%), hepatic transaminase elevation (23%), and hypertension (10%)2
  • ARs reported in at least 2% to <5% of patients taking PONVORY™ and at a higher rate than in patients taking Aubagio® included cough, pain in extremity, somnolence, pyrexia, increase in C-reactive protein, hypercholesterolemia, and vertigo2
  • 82% of patients taking PONVORY™ completed 2 years of study treatment, compared with 82.2% of patients taking Aubagio®2

*Includes the following terms: nasopharyngitis, upper respiratory tract infection, pharyngitis, respiratory tract infection, bronchitis, respiratory tract infection viral, viral upper respiratory tract infection, tracheitis, and laryngitis.2

Includes the following terms: alanine aminotransferase increased, aspartate aminotransferase increased, hepatic enzyme increased, and transaminases increased.2

Includes the following terms: hypertension, hypertensive crisis, blood pressure increased, blood pressure systolic increased, blood pressure diastolic increased.2

Comparable overall rates of TEAEs and SAEs vs Aubagio®1

TEAEs1
PONVORY™
(n = 502)
88.8%
Teriflunomide
(n = 499)
88.2%
SAEs1
PONVORY™
(n = 49)
8.7%
Teriflunomide
(n = 46)
8.1%

Most frequent TEAEs (>5%) in either group3

Most frequent treatment-emergent adverse events (TEAEs)

Among TEAEs, increased ALT, AST, and dyspnea were reported more frequently in patients taking PONVORY™ than in patients taking Aubagio®.3

Diarrhea and alopecia were more frequently reported in patients taking Aubagio®.3

Summary of liver test abnormalities1,2

  • The majority (89%) of patients with alanine aminotransferase (ALT) increases ≥3x the upper limit of normal (ULN) continued treatment with PONVORY™ with values returning to <3x the ULN within approximately 2 to 4 weeks2
  • Most ALT increases ≥3x ULN were single, transient, asymptomatic episodes that resolved on treatment or after protocol-mandated discontinuation1
  • ALT increased ≥3x the ULN in 17.3% of patients taking PONVORY™ compared with 8.3% of patients taking Aubagio®2
  • ALT increased ≥5x ULN in 4.6% of patients taking PONVORY™ compared with 2.5% of patients taking Aubagio®2
  • ALT increased ≥8x ULN in 0.7% of patients taking PONVORY™ compared with 2.1% of patients taking Aubagio®1
  • Patients who develop symptoms suggestive of hepatic dysfunction§ should have hepatic enzymes checked. PONVORY™ should be discontinued if significant liver injury is confirmed2

summary of liver test abnormalities up to EOT + 1 day

ALT = alanine aminotransferase; AST = aspartate aminotransferase; TBIL = total bilirubin; ULN = upper limit of normal.
Central laboratory reference ranges: ALT ULN: 0-44 U/L (male) and 0-33 U/L (female); AST ULN: 14-39 U/L (male) and 14-34 U/L (female).6

§Such as unexplained nausea, vomiting, abdominal pain, fatigue, anorexia, rash with eosinophilia, or jaundice, and/or dark urine during treatment.2

Nn = number of subjects with at least 1 valid treatment-emergent measurement available (from scheduled or unscheduled visit).6

#Patient with preexisting ALT elevation >5x ULN and resolved after discontinuation.1

Effects on heart rate and rhythm on Day 11||

Overview of treatment-emergent heart rate and rhythm (including hypotension) adverse events of special interest, safety set1

effects on heart rate and rhythm on Day 1

First-dose monitoring is recommended for select patients2

Because initiation of PONVORY™ treatment results in a decrease in heart rate (HR), first-dose, 4-hour monitoring is recommended for patients with2:

  • Sinus bradycardia (HR <55 beats per minute [bpm])
  • First- or second-degree atrioventricular (AV) block (Mobitz type I)
  • History of myocardial infarction or heart failure occurring more than 6 months prior to treatment initiation and in stable condition

First-dose monitoring should be completed in a setting where resources to appropriately manage symptomatic bradycardia are available.

In all patients, a dose titration is required for initiation of treatment with PONVORY™ to help reduce cardiac effects2

In the OPTIMUM study:

  • Bradycardia at treatment initiation and sinus bradycardia on ECG** occurred in 5.8% of patients taking PONVORY™ compared with 1.6% of patients taking Aubagio®2
    • Bradycardia resolved in all patients without intervention and did not require discontinuation of treatment2
  • No second- and third-degree AV blocks were observed. AV conduction delays manifested as first-degree AV block (prolonged PR interval on ECG), which occurred in 3.4% of patients taking PONVORY™ and in 1.2% of patients taking Aubagio®2
    • The conduction abnormalities typically were transient, asymptomatic, resolved within 24 hours, resolved without intervention, and did not require discontinuation of treatment with PONVORY™2

AV = atrioventricular; ECG = electrocardiogram.

||These treatment-emergent AESI occurred following the PONVORY™ 2 mg dose on Day 1, consistent with titration requirements for PONVORY™.1,2

**Defined as HR <50 bpm.2

50% of patients remained on PONVORY™ 20 mg4

In the most recent analysis of an ongoing phase 2, long-term, safety extension study4:

50% of patients remained 
on PONVORY™ 20 mg
after 8 years

The median exposure
to PONVORY™ 20 mg
was 8 years

  • The data shown represent patients who initiated PONVORY™ 20 mg treatment in the core study and continued with 20 mg during TP1 of the extension study4

TP = treatment period.

The study period consisted of a core study lasting 24 weeks and an extension study subdivided into 3 TPs. Additional patients received PONVORY™ 10 mg (n = 139) or 40 mg (n = 15) (data not shown). Data were analyzed at the end of TP3 (March 2019). Patients with >8 years of PONVORY™ 20 mg treatment exposure: n = 73; total patients receiving PONVORY™ 20 mg: N = 145.4

As seen in PK-PD assessments, the effects of PONVORY™ on lymphocyte counts are reversible in about 7 days2††

PONVORY™ causes a reversible, dose-dependent reduction in peripheral lymphocyte counts2

  • Lymphocyte counts returned to the normal range in 90% of patients within 1 week of stopping therapy
  • In the OPTIMUM study, peripheral lymphocyte counts returned to the normal range within 2 weeks after discontinuation of PONVORY™, which was the first time point evaluated2
  • Residual PD effects, such as lowering of peripheral lymphocyte counts, may persist for 1 to 2 weeks after discontinuation of PONVORY™

PONVORY™ may increase the risk of infections2:

  • In the OPTIMUM study, the overall rate of infections was comparable between patients taking PONVORY™ and patients taking Aubagio®2
  • Initiation of treatment with PONVORY™ should be delayed in patients with active infections until resolution2
  • Monitor for infection during treatment and for 1 to 2 weeks after discontinuation of PONVORY™2
  • Consider interruption of treatment with PONVORY™ if a patient develops a serious infection2

Vaccine considerations:

  • No clinical data are available on the efficacy and safety of vaccinations in patients taking PONVORY™. Vaccinations may be less effective if administered during PONVORY™ treatment2

For live vaccines:

  • The use of live attenuated vaccines may carry the risk of infection and should therefore be avoided during PONVORY™ treatment and for 1 to 2 weeks after discontinuation of treatment with PONVORY™2
  • PONVORY™ should be paused 1 to 2 weeks prior to and until 4 weeks after a planned vaccination2

For non-live vaccines:

  • No dose adjustment or discontinuation of PONVORY™ treatment was required for non-live vaccinations in the OPTIMUM study5

Your MS patients should always consult with you before receiving any vaccine.

††Severe exacerbation of disease, including disease rebound has been rarely reported after discontinuation of an S1P receptor modulator. The possibility of severe exacerbation of disease should be considered after stopping treatment with PONVORY™. Patients should be observed for a severe increase in disability upon PONVORY™ discontinuation and appropriate treatment should be instituted, as required.2

For more detailed information about infections and vaccinations, please see Section 5 in the PONVORY™ full Prescribing Information.